Topoisomerase targeting with and resistance to gemifloxacin in Staphylococcus aureus

Gemifloxacin, a novel quinolone with potent activity against Staphylococcus aureus, was 8- to 16-fold more active against wild-type S. aureus than ciprofloxacin. The two- to fourfold increase in the MIC of gemifloxacin in genetically defined grlBA mutants and the twofold increase in a single gyrA mutant, supported by the low frequency of selection of resistant mutants at twice the MIC (7.4 x 10(-11) to 1.1 x 10(-10)), suggested similar targeting of the two enzymes by gemifloxacin. Dual mutations in both gyrase and topoisomerase IV caused a 64- to 128-fold increase in the MIC of gemifloxacin, similar to that seen with ciprofloxacin. Gemifloxacin also had similar activity in vitro against topoisomerase IV and gyrase purified from S. aureus (50% inhibitory concentrations of 0.25 and 0.31 micro g/ml, respectively). This activity was 10- to 20-fold higher than that of ciprofloxacin for topoisomerase IV and 33-fold higher than that for gyrase. In contrast to the in vitro findings, only topoisomerase IV mutants were selected in first-step mutants. Overexpression of the NorA efflux pump had a minimal effect on resistance to gemifloxacin, and a mutation in the promoter region of the gene for NorA was selected only in the sixth step of serial selection of mutants. Our data show that although gemifloxacin targets purified topoisomerase IV and gyrase similarly in vitro, topoisomerase IV is the preferred target in the bacteria. Selection of novel resistance mutations in grlA requires further expansion of quinolone-resistance-determining regions, and their study may provide increased insight into enzyme-quinolone interactions.     

The evaluation of safety and efficacy of colistin use in pediatric intensive care unit: Results from two reference hospitals and review of literature

Colistin, an old cationic polypeptide antibiotic, have been reused due to rising incidence of infections caused by multi-drug resistant (MDR) Gram-negative microorganisms and the lack of new antibiotics. Therefore, we evaluated safety and efficacy of colistin in treatment of these infections. This study included 104 critically ill children with a median age of 55,9 months between January 2011 and January 2016. Nephrotoxicity occurred in 11 (10.5%) patients. Nephrotoxicity occurred between the third and seventh day of treatment in 63% of colistin induced nephrotoxicity episodes. The subgroup analysis between the patients who developed nephrotoxicity during colistin treatment and those that did not, showed no significant difference in terms of age, underlying disease, cause for PICU admission and type of infection required colistin treatment, P values were 0.615, 0.762, 0.621, 0.803, respectively. All patients were receiving a concomitant nephrotoxic agent (P = 0,355). The majority of the patients (52%) were having primary or secondary immune deficiency in treatment failure group and the most common cause of PICU admission was sepsis in treatment failure group, P values were 0.007 and 0.045, respectively. Mortality attributed to colistin failure and crude mortality were 14.4% and 29.8%, respectively. In conclusion, colistin may have a role in the treatment of infections caused by multidrug-resistant Gram-negative bacteria in critically ill children. However, the patients have to be followed for side effects throughout colistin treatment, not for only early stage. And the clinicians should be aware of increase in the rate of nephrotoxicity in patients those have been receiving a concomitant nephrotoxic agent.     

Semirigid thoracoscopy in the diagnosis of pleural effusion: first four cases in Turkey

Medical thoracoscopy is a valuable tool in the management and investigation of pleural diseases. It has advantages when compared to conventional closed pleural biopsy and video-assisted thoracoscopic surgery. However, the use of this technique is limited in Turkey. The present report is about the first experience with semi-rigid thoracoscope that was implemented in our country. Four patients underwent medical thoracoscopy in September 2009 with the new device. All patients were referred due to non-diagnostic closed pleural biopsy. The use of the device was simple and fabulous views were obtained. All biopsy specimens of the 4 patients were histologically adequate. Definite diagnosis was enabled in 3 of the 4 patients when clinical features and CT findings combined with thoracoscopic specimens. The design is similar to the fiberoptic bronchoscope, respiratory physicians can easily adapt to its use. It is also compatible with most video operating systems and light sources used in endoscopy suites. The convenient use and compatibility with most endoscopic systems are raising the importance of the device. However, biopsy size from semirigid thoracoscope might cause diagnostic difficulty when compared to rigid thoracoscope.     

Osteoclast-rich undifferentiated carcinomas of the urinary tract.

Osteoclast-like giant-cell neoplasms of the urinary tract are rare. They are composed of ovoid or spindle-shaped mononuclear cells with evenly spaced osteoclast-like giant cells. Terminology, histogenesis, and biologic behavior of these tumors remain controversial. Six cases of osteoclast-like giant-cell neoplasms of the urinary tract were identified from the consultation files of two of the authors. Patients were all male and elderly (range 65-82), with the exception of one 39-year-old male. In all, 3/6 tumors developed in the bladder and 3/6 in the renal pelvis. Size ranged from 5 to 11 cm. One bladder and three renal pelvis tumors were high stage (pT3) at time of presentation. Adjacent to the osteoclast-like giant-cell neoplasm in the same specimen, all patients had urothelial carcinoma in situ and/or high-grade papillary urothelial carcinoma. Multinucleated cells had identical morphological and immunohistochemical properties of osteoclasts; positive for CD-68, LCA, CD51 and CD54, and negative for cytokeratins and EMA. Varying percentages of mononuclear cells expressed alpha-smooth muscle actin (4/6), desmin (1/6), S-100 (4/6), LCA (2/6) and CD68 (6/6). However, mononuclear cells were also positive for epithelial markers in 4/6 tumors (cytokeratins AE-1/AE-3, Cam 5.2, CK7 and/or EMA). p53 stained mononuclear tumor cells in three cases, paralleling the staining on the accompanying urothelial carcinoma. Ki-67 stained mononuclear tumor cells, but not osteoclast-like giant cells. Follow-up data were available in five cases. One patient developed recurrence of noninvasive urothelial carcinoma and is still alive. Four patients were dead due to disease within 15 months, three with distant metastases. The intimate association of these tumors with urothelial carcinoma along with their immunohistochemical profile supports an epithelial origin for the mononuclear cells and non-neoplastic reactive histiocytic lineage for the osteoclast-like giant cells.     

Effect of cervical length on second trimester pregnancy termination

AIM: To evaluate the value of sonographic measurement of cervical length as a predictor of abortion or delivery within 24 h by misoprostol in second trimester termination of pregnancy (TOP). MATERIAL AND METHODS: One hundred and sixty-three women underwent TOP between 14 and 26 weeks of pregnancy due to various indications. The primary outcome was abortion within 24 h. Cervical length was measured before transvaginal administration of misoprostol. The effects of cervical length, total misoprostol dose, parity, and gestational age at diagnosis on successful TOP were evaluated. Results: One hundred and sixty-three women were eligible who met the inclusion criteria. TOP occurred in 80.5% of patients within 24 h. Parous women had shorter prolonged induction to expulsion period over 24 h (14.1% vs 28.6%, P = 0.061). Total misoprostol dose and history of abortion were parameters that affected induction to delivery period (P = 0.002 and P = 0.041). Using an optimum cutoff of 36 mm, 58.2% sensitivity and 68.2% specificity were obtained. In addition, positive and negative predictive values were 85.36% and 33.3%, respectively. Pregnant women whose preinduction cervical length was shorter than 36 mm had a shorter induction time and needed a lower total misoprostol dose to achieve TOP than women with a cervical length longer than 36 mm (P = 0.027 and P = 0.011, respectively). Conclusion: Transvaginal measurement of cervical length before administration of prostaglandin analogue was not correlated with successful TOP within 24 h. It cannot be used as a predictor in light of our findings.     

Use of chemotherapy at the end of life in Turkey

Background

An increasing number of patients receive palliative chemotherapy near the end of life. The aim of this study is to evaluate the aggressiveness of chemotherapy in Turkish individuals near the end of life.

Methods

Patients diagnosed with solid tumors and died from 2010 to 2011 in the medical oncology department of Akdeniz University were included in the study. Data about the diagnosis, treatment details and imaging procedures were collected.

Results

Three hundred and seventy-three people with stage IV solid tumors died from 2010 to 2011 in our clinic. Eighty-nine patients (23.9%) patients underwent chemotherapy in the last month of life while 39 patients (10.5%) received chemotherapy in the last 14 days. The probability of undergoing chemotherapy in the last month of life was influenced by: age, ‘newly diagnosed’ patients, and performance status. There was no significant association of chemotherapy in the last month of life with gender and tumor type. Having a PET-CT scan did not alter the chemotherapy decision.

Conclusion

In conclusion, chemotherapy used in the last month of life in a tertiary care center of Turkey is high. Increasing quality of life should be a priority near the end of life and physicians should consider ceasing chemotherapy and direct the patient to early palliative care.

     

The effect of combined therapy for treatment of monotherapy-resistant PDA in preterm infants

Objective: Hemodynamically significant PDA (hsPDA) is one of the most common problems in preterm infants. This study was conducted to investigate the effect of combined pharmacological (paracetamol?+?ibuprofen) therapy on monotherapy-resistant hsPDA in infants.

Subject and methods: The study included infants with persistent hsPDA, unresponsive to monotherapy. Combined treatment (paracetamol?+?ibuprofen) was started as paracetamol at a dose of 15?mg/kg every 6?hours for 5?days, and ibuprofen at an initial dose of 10?mg/kg followed by 5?mg/kg at 24 and 48?hours. Echocardiographic evaluation was performed at 2?days after the end of treatment. If hsPDA persisted after the combined treatment, a surgical PDA ligation was considered.

Results: A total of 12 infants were enrolled and 9 infants (75%) with monotherapy-resistant PDA were successfully treated with combined therapy. In three patients, no response was obtained to the combined treatment so surgical ligation was applied.

Conclusions: Combined therapy may be a useful treatment option for monotherapy-resistant hsPDA in preterm infants. Before surgical ligations, this combined therapy option should be considered.     

Role of the Neutrophil-Lymphocyte Ratio in the Differential Diagnosis of Exudative Pleural Effusion

OBJECTIVES:Pleural effusion is a common diagnostic and clinical problem. The differential diagnosis of pleural effusion may be difficult and may require several procedures, including invasive ones. Certain studies have investigated biochemical parameters to facilitate the diagnosis of exudative pleural effusion; however, it remains a challenging problem in clinical practice. We aimed to investigate the potential role of the neutrophil-lymphocyte ratio, which can be easily obtained by determining the cell count of the pleural fluid, in the differential diagnosis of exudative pleural effusion.METHODS:Records from patients who underwent thoracentesis and pleural fluid analysis between May 1, 2013, and March 1, 2015, were obtained from the electronic database of our hospital. The patients who met the inclusion criteria were divided into five groups according to their diagnosis: malignant pleural effusion, para-malignant pleural effusion, para-pneumonic effusion, tuberculosis-related effusion or other. The neutrophil-lymphocyte ratio value was calculated by dividing the absolute neutrophil count by the absolute lymphocyte count. The patient groups were compared according to the given parameter.RESULTS:A total of 465 patients who met the inclusion criteria among 1616 patients with exudative pleural effusion were included in the study. The mean neutrophil-lymphocyte ratio value was significantly lower in tuberculosis-related pleural effusion compared to malignant, para-pneumonic and para-malignant effusions (p=0.001, p=0.001, p=0.012, respectively). The areas under the curve for tuberculosis pleurisy compared to malignant, para-pneumonic and para-malignant effusions were 0.38, 0.36, and 0.37, respectively. Lower cut-off values had higher sensitivity but lower specificity for tuberculosis pleurisy, while higher cut-off values had higher specificity but lower sensitivity for this condition.CONCLUSION:The pleural fluid neutrophil-lymphocyte ratio, which is an inexpensive, reproducible, and easily calculated hematological parameter, may facilitate the differential diagnosis of pleural effusion.